MX2015001793A

MX2015001793A - Derivados de benceno sustituidos con arilo y heteroarilo como moduladores de las trayectorias de señalizacion de cinasa pi3.

Derivados de benceno sustituidos con arilo y heteroarilo como moduladores de las trayectorias de señalizacion de cinasa pi3.

Info

Publication number: MX2015001793A
Authority: MX; Mexico
Prior art keywords: phenyl; substituted; alkyl; sulfonyl; thiadiazol
Prior art date: 2012-08-09

Application number

MX2015001793A

Other languages

English (en)

Spanish (es)

Inventor

Wolfgang Wrasidlo

Emily M Stocking

Original Assignee

Neuropore Therapies Inc

Priority date

2012-08-09

Filing date

2013-08-08

Publication date

2015-05-07

2013-08-08 Application filed by Neuropore Therapies Inc filed Critical Neuropore Therapies Inc

2015-05-07 Publication of MX2015001793A publication Critical patent/MX2015001793A/es

Links

125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title abstract description 11
102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 title description 2
108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 title description 2
230000019491 signal transduction Effects 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 61
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 37
201000010099 disease Diseases 0.000 claims abstract description 26
239000008194 pharmaceutical composition Chemical class 0.000 claims abstract description 22
230000004900 autophagic degradation Effects 0.000 claims abstract description 21
230000037361 pathway Effects 0.000 claims abstract description 6
150000001875 compounds Chemical class 0.000 claims description 240
-1 -NRmRn Chemical group 0.000 claims description 148
125000000217 alkyl group Chemical group 0.000 claims description 118
229910052739 hydrogen Inorganic materials 0.000 claims description 59
239000001257 hydrogen Substances 0.000 claims description 56
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 53
229910052736 halogen Inorganic materials 0.000 claims description 52
125000003545 alkoxy group Chemical group 0.000 claims description 51
150000003839 salts Chemical class 0.000 claims description 48
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 43
150000002367 halogens Chemical group 0.000 claims description 42
125000002947 alkylene group Chemical group 0.000 claims description 41
238000011282 treatment Methods 0.000 claims description 39
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 37
125000000753 cycloalkyl group Chemical group 0.000 claims description 28
LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 28
125000001424 substituent group Chemical group 0.000 claims description 28
229910052757 nitrogen Inorganic materials 0.000 claims description 27
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 24
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 21
125000004093 cyano group Chemical group *C#N 0.000 claims description 21
125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 claims description 19
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 17
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 10
125000004438 haloalkoxy group Chemical group 0.000 claims description 9
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 8
239000000546 pharmaceutical excipient Substances 0.000 claims description 8
125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 7
208000024827 Alzheimer disease Diseases 0.000 claims description 7
125000001188 haloalkyl group Chemical group 0.000 claims description 7
208000018737 Parkinson disease Diseases 0.000 claims description 6
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 6
125000002883 imidazolyl group Chemical group 0.000 claims description 6
125000000168 pyrrolyl group Chemical group 0.000 claims description 6
206010012289 Dementia Diseases 0.000 claims description 5
208000023105 Huntington disease Diseases 0.000 claims description 5
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
201000002832 Lewy body dementia Diseases 0.000 claims description 5
125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
125000002541 furyl group Chemical group 0.000 claims description 5
208000015181 infectious disease Diseases 0.000 claims description 5
125000003831 tetrazolyl group Chemical group 0.000 claims description 5
125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
125000000335 thiazolyl group Chemical group 0.000 claims description 5
125000001425 triazolyl group Chemical group 0.000 claims description 5
125000001544 thienyl group Chemical group 0.000 claims description 4
125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 3
208000011231 Crohn disease Diseases 0.000 claims description 3
201000011240 Frontotemporal dementia Diseases 0.000 claims description 3
206010028980 Neoplasm Diseases 0.000 claims description 3
230000032683 aging Effects 0.000 claims description 3
201000011510 cancer Diseases 0.000 claims description 3
208000019622 heart disease Diseases 0.000 claims description 3
125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
125000002971 oxazolyl group Chemical group 0.000 claims description 3
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
230000009885 systemic effect Effects 0.000 claims description 3
METQSAABMLHWQI-UHFFFAOYSA-N (4-chlorophenyl)-[4-(1,3,4-thiadiazol-2-ylamino)phenyl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)C(C=C1)=CC=C1NC1=NN=CS1 METQSAABMLHWQI-UHFFFAOYSA-N 0.000 claims description 2
POVLEEZLVJLEBQ-UHFFFAOYSA-N 2-[5-[[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]amino]-1,3,4-thiadiazol-2-yl]ethanol Chemical compound S1C(CCO)=NN=C1NC1=CN=C(S(=O)(=O)C=2C=CC(Cl)=CC=2)C=N1 POVLEEZLVJLEBQ-UHFFFAOYSA-N 0.000 claims description 2
206010003694 Atrophy Diseases 0.000 claims description 2
206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 2
HKUJIISFLUFFCV-UHFFFAOYSA-N [4-chloro-3-(trifluoromethyl)phenyl]-[4-(1,3,4-thiadiazol-2-ylamino)phenyl]methanone Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(C(=O)C=2C=CC(NC=3SC=NN=3)=CC=2)=C1 HKUJIISFLUFFCV-UHFFFAOYSA-N 0.000 claims description 2
230000037444 atrophy Effects 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims 4
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
WMIYGLJKCSOJFI-UHFFFAOYSA-N 1-n-[4-chloro-3-(trifluoromethyl)phenyl]-4-n-(1,3,4-thiadiazol-2-yl)benzene-1,4-diamine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(NC=2C=CC(NC=3SC=NN=3)=CC=2)=C1 WMIYGLJKCSOJFI-UHFFFAOYSA-N 0.000 claims 1
YHWARMRGGTVWMO-UHFFFAOYSA-N 5-(aziridin-1-ylmethyl)-n-[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C(N=C1)=CN=C1NC(S1)=NN=C1CN1CC1 YHWARMRGGTVWMO-UHFFFAOYSA-N 0.000 claims 1
208000034189 Sclerosis Diseases 0.000 claims 1
GUNNOKLWFBJUQO-UHFFFAOYSA-N n-[2-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylpyrimidin-5-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2N=CC(NC=3SC=NN=3)=CN=2)=C1 GUNNOKLWFBJUQO-UHFFFAOYSA-N 0.000 claims 1
YUVKNKMPXOKAQO-UHFFFAOYSA-N n-[2-chloro-4-[3-(trifluoromethyl)phenyl]sulfonylphenyl]-1,3,4-thiadiazol-2-amine Chemical compound FC(F)(F)C1=CC=CC(S(=O)(=O)C=2C=C(Cl)C(NC=3SC=NN=3)=CC=2)=C1 YUVKNKMPXOKAQO-UHFFFAOYSA-N 0.000 claims 1
KXSGSZSNBGOCDY-UHFFFAOYSA-N n-[3-[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl-1,2,4-triazin-6-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2N=NC(NC=3SC=NN=3)=CN=2)=C1 KXSGSZSNBGOCDY-UHFFFAOYSA-N 0.000 claims 1
TXNOSKGLWXEJOQ-UHFFFAOYSA-N n-[4-(2-chloro-4-fluorophenyl)sulfonylphenyl]-1,3,4-thiadiazol-2-amine Chemical compound ClC1=CC(F)=CC=C1S(=O)(=O)C(C=C1)=CC=C1NC1=NN=CS1 TXNOSKGLWXEJOQ-UHFFFAOYSA-N 0.000 claims 1
JJBRYZUGWJJTPU-UHFFFAOYSA-N n-[4-(4-fluorophenyl)sulfonylphenyl]-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(F)=CC=C1S(=O)(=O)C(C=C1)=CC=C1NC1=NN=CS1 JJBRYZUGWJJTPU-UHFFFAOYSA-N 0.000 claims 1
SZGLXKSNLYOORR-UHFFFAOYSA-N n-[4-[3-(trifluoromethoxy)phenyl]sulfonylphenyl]-1,3,4-thiadiazol-2-amine Chemical compound FC(F)(F)OC1=CC=CC(S(=O)(=O)C=2C=CC(NC=3SC=NN=3)=CC=2)=C1 SZGLXKSNLYOORR-UHFFFAOYSA-N 0.000 claims 1
KAQZQFPYKRJGSK-UHFFFAOYSA-N n-[4-[3-(trifluoromethyl)phenyl]sulfonylphenyl]-1,3,4-thiadiazol-2-amine Chemical compound FC(F)(F)C1=CC=CC(S(=O)(=O)C=2C=CC(NC=3SC=NN=3)=CC=2)=C1 KAQZQFPYKRJGSK-UHFFFAOYSA-N 0.000 claims 1
PHYYVLXFAQCOLF-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl-3-fluorophenyl]-1,3,4-thiadiazol-2-amine Chemical compound C=1C=C(S(=O)(=O)C=2C=C(C(Cl)=CC=2)C(F)(F)F)C(F)=CC=1NC1=NN=CS1 PHYYVLXFAQCOLF-UHFFFAOYSA-N 0.000 claims 1
YVUIQHKJPBSQSU-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylphenyl]-1,3,4-oxadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2C=CC(NC=3OC=NN=3)=CC=2)=C1 YVUIQHKJPBSQSU-UHFFFAOYSA-N 0.000 claims 1
SZOPGUATBWMHNR-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylphenyl]-1h-1,2,4-triazol-5-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2C=CC(NC=3NN=CN=3)=CC=2)=C1 SZOPGUATBWMHNR-UHFFFAOYSA-N 0.000 claims 1
FFPBFHRJGZTMQU-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylphenyl]-1h-imidazol-5-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2C=CC(NC=3NC=NC=3)=CC=2)=C1 FFPBFHRJGZTMQU-UHFFFAOYSA-N 0.000 claims 1
AXWHUZXBRSKCLL-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylphenyl]-1h-pyrrol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2C=CC(NC=3NC=CC=3)=CC=2)=C1 AXWHUZXBRSKCLL-UHFFFAOYSA-N 0.000 claims 1
URTSUAFRXCZONN-UHFFFAOYSA-N n-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylphenyl]-2h-tetrazol-5-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2C=CC(NC3=NNN=N3)=CC=2)=C1 URTSUAFRXCZONN-UHFFFAOYSA-N 0.000 claims 1
SKFKQHGEQGJBPF-UHFFFAOYSA-N n-[4-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]phenyl]-1,3,4-thiadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(CC=2C=CC(NC=3SC=NN=3)=CC=2)=C1 SKFKQHGEQGJBPF-UHFFFAOYSA-N 0.000 claims 1
JGXKXZOVOZYZTI-UHFFFAOYSA-N n-[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C(N=C1)=CN=C1NC1=NN=CS1 JGXKXZOVOZYZTI-UHFFFAOYSA-N 0.000 claims 1
IQIARBSSAQBFHI-UHFFFAOYSA-N n-[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]-5-(morpholin-4-ylmethyl)-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C(N=C1)=CN=C1NC(S1)=NN=C1CN1CCOCC1 IQIARBSSAQBFHI-UHFFFAOYSA-N 0.000 claims 1
HXQHDPILLFXWCT-UHFFFAOYSA-N n-[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]-5-(piperidin-1-ylmethyl)-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C(N=C1)=CN=C1NC(S1)=NN=C1CN1CCCCC1 HXQHDPILLFXWCT-UHFFFAOYSA-N 0.000 claims 1
CXKMZZFUCHIDLF-UHFFFAOYSA-N n-[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]-5-[(4-methylpiperazin-1-yl)methyl]-1,3,4-thiadiazol-2-amine Chemical compound C1CN(C)CCN1CC(S1)=NN=C1NC1=CN=C(S(=O)(=O)C=2C=CC(Cl)=CC=2)C=N1 CXKMZZFUCHIDLF-UHFFFAOYSA-N 0.000 claims 1
SCKSIULALHNVKP-UHFFFAOYSA-N n-[5-(4-fluorophenyl)sulfonylpyrazin-2-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(F)=CC=C1S(=O)(=O)C(N=C1)=CN=C1NC1=NN=CS1 SCKSIULALHNVKP-UHFFFAOYSA-N 0.000 claims 1
KYUNDAOKBURETM-UHFFFAOYSA-N n-[5-[4-(trifluoromethoxy)phenyl]sulfonylpyrazin-2-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=CC(OC(F)(F)F)=CC=C1S(=O)(=O)C(N=C1)=CN=C1NC1=NN=CS1 KYUNDAOKBURETM-UHFFFAOYSA-N 0.000 claims 1
CYNPWXCNCPZFOB-UHFFFAOYSA-N n-[5-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylpyrazin-2-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2N=CC(NC=3SC=NN=3)=NC=2)=C1 CYNPWXCNCPZFOB-UHFFFAOYSA-N 0.000 claims 1
SDMIDNGLYTZDHC-UHFFFAOYSA-N n-[6-[4-chloro-3-(trifluoromethyl)phenyl]sulfonyl-1,2,4,5-tetrazin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2N=NC(NC=3SC=NN=3)=NN=2)=C1 SDMIDNGLYTZDHC-UHFFFAOYSA-N 0.000 claims 1
QMXJMPRWYDCXCG-UHFFFAOYSA-N n-[6-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylpyridin-3-yl]-1,3,4-thiadiazol-2-amine Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2N=CC(NC=3SC=NN=3)=CC=2)=C1 QMXJMPRWYDCXCG-UHFFFAOYSA-N 0.000 claims 1
PUCFTQBPVTZKNA-UHFFFAOYSA-N n-[[5-[[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]amino]-1,3,4-thiadiazol-2-yl]methyl]methanesulfonamide Chemical compound S1C(CNS(=O)(=O)C)=NN=C1NC1=CN=C(S(=O)(=O)C=2C=CC(Cl)=CC=2)C=N1 PUCFTQBPVTZKNA-UHFFFAOYSA-N 0.000 claims 1
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 1
230000002401 inhibitory effect Effects 0.000 abstract description 5
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 113
238000006243 chemical reaction Methods 0.000 description 106
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 61
239000000203 mixture Substances 0.000 description 59
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
125000003118 aryl group Chemical group 0.000 description 40
125000001072 heteroaryl group Chemical group 0.000 description 40
235000019439 ethyl acetate Nutrition 0.000 description 38
125000000623 heterocyclic group Chemical group 0.000 description 36
125000000392 cycloalkenyl group Chemical group 0.000 description 29
229910001868 water Inorganic materials 0.000 description 26
239000003208 petroleum Substances 0.000 description 25
239000007787 solid Substances 0.000 description 24
239000000243 solution Substances 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
210000004027 cell Anatomy 0.000 description 23
125000000547 substituted alkyl group Chemical group 0.000 description 20
238000004809 thin layer chromatography Methods 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
235000019441 ethanol Nutrition 0.000 description 17
238000012544 monitoring process Methods 0.000 description 17
239000012044 organic layer Substances 0.000 description 17
125000003107 substituted aryl group Chemical group 0.000 description 17
238000003786 synthesis reaction Methods 0.000 description 17
125000000304 alkynyl group Chemical group 0.000 description 16
230000015572 biosynthetic process Effects 0.000 description 16
239000003814 drug Substances 0.000 description 16
208000024891 symptom Diseases 0.000 description 16
125000005843 halogen group Chemical group 0.000 description 15
125000005842 heteroatom Chemical group 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
125000003342 alkenyl group Chemical group 0.000 description 14
229910052799 carbon Inorganic materials 0.000 description 14
125000004432 carbon atom Chemical group C* 0.000 description 14
230000008569 process Effects 0.000 description 14
108090000623 proteins and genes Proteins 0.000 description 14
125000005346 substituted cycloalkyl group Chemical group 0.000 description 14
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
229940079593 drug Drugs 0.000 description 12
239000000651 prodrug Substances 0.000 description 12
229940002612 prodrug Drugs 0.000 description 12
102000004169 proteins and genes Human genes 0.000 description 12
125000005017 substituted alkenyl group Chemical group 0.000 description 12
125000004426 substituted alkynyl group Chemical group 0.000 description 12
238000012360 testing method Methods 0.000 description 12
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
239000002253 acid Substances 0.000 description 11
208000035475 disorder Diseases 0.000 description 11
208000015122 neurodegenerative disease Diseases 0.000 description 11
235000018102 proteins Nutrition 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
125000004429 atom Chemical group 0.000 description 10
238000005481 NMR spectroscopy Methods 0.000 description 9
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 9
125000003277 amino group Chemical group 0.000 description 9
239000000460 chlorine Chemical group 0.000 description 9
238000005516 engineering process Methods 0.000 description 9
150000002500 ions Chemical class 0.000 description 9
238000010992 reflux Methods 0.000 description 9
229910052717 sulfur Inorganic materials 0.000 description 9
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
239000004480 active ingredient Substances 0.000 description 8
125000002252 acyl group Chemical group 0.000 description 8
239000003795 chemical substances by application Substances 0.000 description 8
125000005283 haloketone group Chemical group 0.000 description 8
229910052760 oxygen Inorganic materials 0.000 description 8
238000002360 preparation method Methods 0.000 description 8
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea group Chemical group NC(=S)N UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 8
102000013455 Amyloid beta-Peptides Human genes 0.000 description 7
108010090849 Amyloid beta-Peptides Proteins 0.000 description 7
239000013543 active substance Substances 0.000 description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
239000012267 brine Substances 0.000 description 7
125000001309 chloro group Chemical group Cl* 0.000 description 7
125000001153 fluoro group Chemical group F* 0.000 description 7
230000007246 mechanism Effects 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
239000000047 product Substances 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
125000005309 thioalkoxy group Chemical group 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
125000004122 cyclic group Chemical group 0.000 description 6
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
230000000694 effects Effects 0.000 description 6
230000014509 gene expression Effects 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
239000000463 material Substances 0.000 description 6
150000007522 mineralic acids Chemical class 0.000 description 6
230000004770 neurodegeneration Effects 0.000 description 6
150000007524 organic acids Chemical class 0.000 description 6
239000001301 oxygen Substances 0.000 description 6
239000012453 solvate Substances 0.000 description 6
239000000126 substance Substances 0.000 description 6
238000006467 substitution reaction Methods 0.000 description 6
239000011593 sulfur Chemical group 0.000 description 6
239000007832 Na2SO4 Substances 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
239000012043 crude product Substances 0.000 description 5
125000000524 functional group Chemical group 0.000 description 5
125000001183 hydrocarbyl group Chemical group 0.000 description 5
230000001965 increasing effect Effects 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
239000012038 nucleophile Substances 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
230000003647 oxidation Effects 0.000 description 5
238000007254 oxidation reaction Methods 0.000 description 5
239000002243 precursor Substances 0.000 description 5
239000011734 sodium Substances 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 5
230000004083 survival effect Effects 0.000 description 5
150000003573 thiols Chemical class 0.000 description 5
125000004953 trihalomethyl group Chemical group 0.000 description 5
125000003161 (C1-C6) alkylene group Chemical group 0.000 description 4
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
208000001089 Multiple system atrophy Diseases 0.000 description 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 4
108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 4
125000004442 acylamino group Chemical group 0.000 description 4
125000004423 acyloxy group Chemical group 0.000 description 4
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
230000002776 aggregation Effects 0.000 description 4
238000004220 aggregation Methods 0.000 description 4
125000000266 alpha-aminoacyl group Chemical group 0.000 description 4
125000004104 aryloxy group Chemical group 0.000 description 4
238000003556 assay Methods 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
230000001413 cellular effect Effects 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
230000018109 developmental process Effects 0.000 description 4
ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
235000003599 food sweetener Nutrition 0.000 description 4
238000009472 formulation Methods 0.000 description 4
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
125000005553 heteroaryloxy group Chemical group 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
239000010410 layer Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
239000002207 metabolite Substances 0.000 description 4
DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
238000002600 positron emission tomography Methods 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
238000002603 single-photon emission computed tomography Methods 0.000 description 4
239000003765 sweetening agent Substances 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
125000005296 thioaryloxy group Chemical group 0.000 description 4
125000005404 thioheteroaryloxy group Chemical group 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
150000003852 triazoles Chemical class 0.000 description 4
239000003981 vehicle Substances 0.000 description 4
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 3
VSZQSTUDNPQHCA-UHFFFAOYSA-N 4-chloro-3-(trifluoromethyl)benzenethiol Chemical compound FC(F)(F)C1=CC(S)=CC=C1Cl VSZQSTUDNPQHCA-UHFFFAOYSA-N 0.000 description 3
101710137189 Amyloid-beta A4 protein Proteins 0.000 description 3
101710151993 Amyloid-beta precursor protein Proteins 0.000 description 3
102100022704 Amyloid-beta precursor protein Human genes 0.000 description 3
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 3
238000002965 ELISA Methods 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 3
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
208000009829 Lewy Body Disease Diseases 0.000 description 3
241000124008 Mammalia Species 0.000 description 3
206010029260 Neuroblastoma Diseases 0.000 description 3
229910019142 PO4 Inorganic materials 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
230000003213 activating effect Effects 0.000 description 3
239000003513 alkali Substances 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 3
239000003963 antioxidant agent Substances 0.000 description 3
235000006708 antioxidants Nutrition 0.000 description 3
210000004957 autophagosome Anatomy 0.000 description 3
239000002585 base Substances 0.000 description 3
230000008901 benefit Effects 0.000 description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
125000001246 bromo group Chemical group Br* 0.000 description 3
239000002775 capsule Substances 0.000 description 3
150000001768 cations Chemical class 0.000 description 3
125000003636 chemical group Chemical group 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
230000000295 complement effect Effects 0.000 description 3
230000008878 coupling Effects 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
230000007423 decrease Effects 0.000 description 3
238000013461 design Methods 0.000 description 3
238000011161 development Methods 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
229960003638 dopamine Drugs 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
239000012091 fetal bovine serum Substances 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
239000012458 free base Substances 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
239000005090 green fluorescent protein Substances 0.000 description 3
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
239000005457 ice water Substances 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000002372 labelling Methods 0.000 description 3
230000000670 limiting effect Effects 0.000 description 3
239000000314 lubricant Substances 0.000 description 3
LDDHMLJTFXJGPI-UHFFFAOYSA-N memantine hydrochloride Chemical compound Cl.C1C(C2)CC3(C)CC1(C)CC2(N)C3 LDDHMLJTFXJGPI-UHFFFAOYSA-N 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
238000007344 nucleophilic reaction Methods 0.000 description 3
235000021317 phosphate Nutrition 0.000 description 3
150000003013 phosphoric acid derivatives Chemical class 0.000 description 3
229920001515 polyalkylene glycol Polymers 0.000 description 3
238000002953 preparative HPLC Methods 0.000 description 3
230000003449 preventive effect Effects 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
238000000746 purification Methods 0.000 description 3
150000003254 radicals Chemical class 0.000 description 3
ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 3
230000015629 regulation of autophagy Effects 0.000 description 3
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 3
QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
229960002930 sirolimus Drugs 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
229940032147 starch Drugs 0.000 description 3
230000004936 stimulating effect Effects 0.000 description 3
125000005415 substituted alkoxy group Chemical group 0.000 description 3
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 3
239000000725 suspension Substances 0.000 description 3
239000003826 tablet Substances 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
150000003536 tetrazoles Chemical class 0.000 description 3
125000003396 thiol group Chemical group [H]S* 0.000 description 3
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 3
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 2
SYTBZMRGLBWNTM-SNVBAGLBSA-N (R)-flurbiprofen Chemical compound FC1=CC([C@H](C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-SNVBAGLBSA-N 0.000 description 2
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
SNKZJIOFVMKAOJ-UHFFFAOYSA-N 3-Aminopropanesulfonate Chemical compound NCCCS(O)(=O)=O SNKZJIOFVMKAOJ-UHFFFAOYSA-N 0.000 description 2
ONNMDRQRSGKZCN-UHFFFAOYSA-N 3-aminopropyl(butyl)phosphinic acid Chemical compound CCCCP(O)(=O)CCCN ONNMDRQRSGKZCN-UHFFFAOYSA-N 0.000 description 2
LADGTIIIXLYISM-UHFFFAOYSA-N 4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylaniline Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(Cl)C(C(F)(F)F)=C1 LADGTIIIXLYISM-UHFFFAOYSA-N 0.000 description 2
AXBVSRMHOPMXBA-UHFFFAOYSA-N 4-nitrothiophenol Chemical compound [O-][N+](=O)C1=CC=C(S)C=C1 AXBVSRMHOPMXBA-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
239000002126 C01EB10 - Adenosine Substances 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
MQHWFIOJQSCFNM-UHFFFAOYSA-L Magnesium salicylate Chemical compound [Mg+2].OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O MQHWFIOJQSCFNM-UHFFFAOYSA-L 0.000 description 2
150000001204 N-oxides Chemical class 0.000 description 2
208000012902 Nervous system disease Diseases 0.000 description 2
208000025966 Neurological disease Diseases 0.000 description 2
102000038030 PI3Ks Human genes 0.000 description 2
108091007960 PI3Ks Proteins 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
235000021355 Stearic acid Nutrition 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
150000001266 acyl halides Chemical class 0.000 description 2
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
229960005305 adenosine Drugs 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
150000001336 alkenes Chemical class 0.000 description 2
150000001345 alkine derivatives Chemical class 0.000 description 2
125000000033 alkoxyamino group Chemical group 0.000 description 2
125000002877 alkyl aryl group Chemical group 0.000 description 2
125000003368 amide group Chemical group 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
238000006254 arylation reaction Methods 0.000 description 2
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 2
MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
230000033228 biological regulation Effects 0.000 description 2
WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 2
229910000024 caesium carbonate Inorganic materials 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000003543 catechol methyltransferase inhibitor Substances 0.000 description 2
230000005754 cellular signaling Effects 0.000 description 2
239000000544 cholinesterase inhibitor Substances 0.000 description 2
239000000470 constituent Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
125000006165 cyclic alkyl group Chemical group 0.000 description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
230000003412 degenerative effect Effects 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
238000001514 detection method Methods 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
238000009509 drug development Methods 0.000 description 2
239000003623 enhancer Substances 0.000 description 2
238000003818 flash chromatography Methods 0.000 description 2
UQSQSQZYBQSBJZ-UHFFFAOYSA-M fluorosulfonate Chemical compound [O-]S(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-M 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
239000008187 granular material Substances 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
230000035876 healing Effects 0.000 description 2
IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
230000007774 longterm Effects 0.000 description 2
229920001427 mPEG Polymers 0.000 description 2
229940072082 magnesium salicylate Drugs 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
229960004640 memantine Drugs 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
125000002757 morpholinyl group Chemical group 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
239000004090 neuroprotective agent Substances 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
210000003463 organelle Anatomy 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 2
239000012071 phase Substances 0.000 description 2
RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
230000026731 phosphorylation Effects 0.000 description 2
238000006366 phosphorylation reaction Methods 0.000 description 2
229920000642 polymer Polymers 0.000 description 2
229920001451 polypropylene glycol Polymers 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000000843 powder Substances 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
238000011002 quantification Methods 0.000 description 2
230000009467 reduction Effects 0.000 description 2
238000006722 reduction reaction Methods 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
238000009256 replacement therapy Methods 0.000 description 2
125000006413 ring segment Chemical group 0.000 description 2
229960001860 salicylate Drugs 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
239000008117 stearic acid Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
150000003462 sulfoxides Chemical class 0.000 description 2
239000000829 suppository Substances 0.000 description 2
230000001629 suppression Effects 0.000 description 2
229960001685 tacrine Drugs 0.000 description 2
ZMZDMBWJUHKJPS-UHFFFAOYSA-M thiocyanate group Chemical group [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 2
125000004568 thiomorpholinyl group Chemical group 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
230000009466 transformation Effects 0.000 description 2
238000000844 transformation Methods 0.000 description 2
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 2
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
229910052727 yttrium Inorganic materials 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
HCLIFWZTTKDJGO-ZOWNYOTGSA-N (1r)-1-(1-benzothiophen-5-yl)-2-[2-(dimethylamino)ethoxy]ethanol;hydrochloride Chemical compound Cl.CN(C)CCOC[C@H](O)C1=CC=C2SC=CC2=C1 HCLIFWZTTKDJGO-ZOWNYOTGSA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 description 1
VBRJFXSFCYEZMQ-HNNXBMFYSA-N (2s)-2-amino-3-[3-(2-chlorophenyl)-5-(phosphonomethyl)phenyl]propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC(CP(O)(O)=O)=CC(C=2C(=CC=CC=2)Cl)=C1 VBRJFXSFCYEZMQ-HNNXBMFYSA-N 0.000 description 1
NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
AVOAYDGOIVBXMW-UHFFFAOYSA-N 1-amino-3-[4-[4-chloro-3-(trifluoromethyl)phenyl]sulfonylphenyl]thiourea Chemical compound C1=CC(NC(=S)NN)=CC=C1S(=O)(=O)C1=CC=C(Cl)C(C(F)(F)F)=C1 AVOAYDGOIVBXMW-UHFFFAOYSA-N 0.000 description 1
FOTLYDRVDFFNIJ-UHFFFAOYSA-N 1-chloro-4-(4-isothiocyanatophenyl)sulfonyl-2-(trifluoromethyl)benzene Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(S(=O)(=O)C=2C=CC(=CC=2)N=C=S)=C1 FOTLYDRVDFFNIJ-UHFFFAOYSA-N 0.000 description 1
CIQJWKNJDQKPPO-UHFFFAOYSA-N 1-chloropiperidine Chemical compound ClN1CCCCC1 CIQJWKNJDQKPPO-UHFFFAOYSA-N 0.000 description 1
LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
ZZAKLGGGMWORRT-UHFFFAOYSA-N 1-methylsulfonylpiperazine Chemical compound CS(=O)(=O)N1CCNCC1 ZZAKLGGGMWORRT-UHFFFAOYSA-N 0.000 description 1
LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical class OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
125000003163 2-(2-naphthyl)ethyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(C([H])=C([H])C2=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
SSORSZACHCNXSJ-UHFFFAOYSA-N 2-[2-(3,4-dichlorophenyl)-3-[2-(2-hydroxypropylamino)pyrimidin-4-yl]imidazol-4-yl]acetonitrile Chemical compound ClC=1C=C(C=CC=1Cl)C=1N(C(=CN=1)CC#N)C1=NC(=NC=C1)NCC(C)O SSORSZACHCNXSJ-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical class OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
NIRHKQWWUBHGOI-UHFFFAOYSA-N 2-fluoro-5,6-dimethoxy-2,3-dihydroinden-1-one Chemical compound C1=C(OC)C(OC)=CC2=C1C(=O)C(F)C2 NIRHKQWWUBHGOI-UHFFFAOYSA-N 0.000 description 1
VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 1
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
CWEHWZPCDBRUNO-WLHGVMLRSA-N 3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1h-1-benzazepin-8-yl)propan-1-one;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C=1C=C2CCCCNC2=CC=1C(=O)CCC(CC1)CCN1CC1=CC=CC=C1 CWEHWZPCDBRUNO-WLHGVMLRSA-N 0.000 description 1
DNFGPFRQSJOKEZ-UHFFFAOYSA-N 3-[2-(1-benzylpiperidin-4-yl)ethyl]-2,5-dihydropyrrolo[3,2-f][1,2]benzoxazol-6-one Chemical compound N1OC2=CC3=NC(=O)CC3=CC2=C1CCC(CC1)CCN1CC1=CC=CC=C1 DNFGPFRQSJOKEZ-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
UZJBHDNDSWAPQK-UHFFFAOYSA-N 3-ethoxy-3-iminopropanoic acid;hydrochloride Chemical compound Cl.CCOC(=N)CC(O)=O UZJBHDNDSWAPQK-UHFFFAOYSA-N 0.000 description 1
125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 description 1
CBKDCOKSXCTDAA-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzothiophene Chemical compound C1CCCC2=C1C=CS2 CBKDCOKSXCTDAA-UHFFFAOYSA-N 0.000 description 1
AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
CSGQAXNJZHDONX-UHFFFAOYSA-N 4-methyl-6-phenyl-3-(4-pyrimidin-2-ylpiperazin-1-yl)pyridazine;dihydrochloride Chemical compound Cl.Cl.CC1=CC(C=2C=CC=CC=2)=NN=C1N(CC1)CCN1C1=NC=CC=N1 CSGQAXNJZHDONX-UHFFFAOYSA-N 0.000 description 1
CEWQJIXZGRVCBB-UHFFFAOYSA-N 4-methyl-6-phenyl-3-(4-pyrimidin-2-ylpiperazin-1-yl)pyridazine;hydrate;dihydrochloride Chemical compound O.Cl.Cl.CC1=CC(C=2C=CC=CC=2)=NN=C1N(CC1)CCN1C1=NC=CC=N1 CEWQJIXZGRVCBB-UHFFFAOYSA-N 0.000 description 1
239000005725 8-Hydroxyquinoline Substances 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
235000019489 Almond oil Nutrition 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
102000009091 Amyloidogenic Proteins Human genes 0.000 description 1
108010048112 Amyloidogenic Proteins Proteins 0.000 description 1
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical class NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
241001250138 Arilus Species 0.000 description 1
238000000035 BCA protein assay Methods 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical class C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
MNIPYSSQXLZQLJ-UHFFFAOYSA-N Biofenac Chemical compound OC(=O)COC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl MNIPYSSQXLZQLJ-UHFFFAOYSA-N 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
102100040999 Catechol O-methyltransferase Human genes 0.000 description 1
108020002739 Catechol O-methyltransferase Proteins 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
QCDFBFJGMNKBDO-UHFFFAOYSA-N Clioquinol Chemical compound C1=CN=C2C(O)=C(I)C=C(Cl)C2=C1 QCDFBFJGMNKBDO-UHFFFAOYSA-N 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 1
238000007022 Delepine synthesis reaction Methods 0.000 description 1
238000010466 Delépine reaction Methods 0.000 description 1
208000006558 Dental Calculus Diseases 0.000 description 1
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
238000012286 ELISA Assay Methods 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
230000005526 G1 to G0 transition Effects 0.000 description 1
229930182566 Gentamicin Natural products 0.000 description 1
CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
ZRJBHWIHUMBLCN-SEQYCRGISA-N Huperzine A Natural products N1C(=O)C=CC2=C1C[C@H]1/C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-SEQYCRGISA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
239000005909 Kieselgur Substances 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
SRBFZHDQGSBBOR-OWMBCFKOSA-N L-ribopyranose Chemical compound O[C@H]1COC(O)[C@@H](O)[C@H]1O SRBFZHDQGSBBOR-OWMBCFKOSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
239000005639 Lauric acid Substances 0.000 description 1
241000713666 Lentivirus Species 0.000 description 1
108010000817 Leuprolide Proteins 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 1
ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
102000029749 Microtubule Human genes 0.000 description 1
108091022875 Microtubule Proteins 0.000 description 1
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 1
CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical class COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
102000004316 Oxidoreductases Human genes 0.000 description 1
108090000854 Oxidoreductases Proteins 0.000 description 1
235000021314 Palmitic acid Nutrition 0.000 description 1
229930040373 Paraformaldehyde Natural products 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
IGVPBCZDHMIOJH-UHFFFAOYSA-N Phenyl butyrate Chemical class CCCC(=O)OC1=CC=CC=C1 IGVPBCZDHMIOJH-UHFFFAOYSA-N 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
ZRJBHWIHUMBLCN-UHFFFAOYSA-N Shuangyiping Natural products N1C(=O)C=CC2=C1CC1C(=CC)C2(N)CC(C)=C1 ZRJBHWIHUMBLCN-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
239000005708 Sodium hypochlorite Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
238000006069 Suzuki reaction reaction Methods 0.000 description 1
102000019355 Synuclein Human genes 0.000 description 1
108050006783 Synuclein Proteins 0.000 description 1
DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 description 1
QKDLQFSLLCQTOH-UHFFFAOYSA-N Trichodonin Natural products C1C(O)C2C3(COC(=O)C)C(C=O)C(C)(C)CCC3OC(=O)C22C(=O)C(=C)C1C2 QKDLQFSLLCQTOH-UHFFFAOYSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000007244 Zea mays Nutrition 0.000 description 1
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
229960004420 aceclofenac Drugs 0.000 description 1
FSQKKOOTNAMONP-UHFFFAOYSA-N acemetacin Chemical compound CC1=C(CC(=O)OCC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 FSQKKOOTNAMONP-UHFFFAOYSA-N 0.000 description 1
229960004892 acemetacin Drugs 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
QXRLZDPMLKYXHA-UHFFFAOYSA-N acetic acid oxaldehydic acid Chemical compound C(C=O)(=O)O.C(C)(=O)O QXRLZDPMLKYXHA-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
229960001138 acetylsalicylic acid Drugs 0.000 description 1
150000001252 acrylic acid derivatives Chemical class 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000012190 activator Substances 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
239000008168 almond oil Substances 0.000 description 1
229940061720 alpha hydroxy acid Drugs 0.000 description 1
150000001280 alpha hydroxy acids Chemical class 0.000 description 1
102000003802 alpha-Synuclein Human genes 0.000 description 1
108090000185 alpha-Synuclein Proteins 0.000 description 1
VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
230000004075 alteration Effects 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
229940063655 aluminum stearate Drugs 0.000 description 1
238000005910 aminocarbonylation reaction Methods 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
229940111133 antiinflammatory and antirheumatic drug oxicams Drugs 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
229940039856 aricept Drugs 0.000 description 1
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
WOIIIUDZSOLAIW-NSHDSACASA-N azapropazone Chemical compound C1=C(C)C=C2N3C(=O)[C@H](CC=C)C(=O)N3C(N(C)C)=NC2=C1 WOIIIUDZSOLAIW-NSHDSACASA-N 0.000 description 1
229960001671 azapropazone Drugs 0.000 description 1
XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
125000002785 azepinyl group Chemical group 0.000 description 1
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
230000003385 bacteriostatic effect Effects 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
FEJKLNWAOXSSNR-UHFFFAOYSA-N benorilate Chemical compound C1=CC(NC(=O)C)=CC=C1OC(=O)C1=CC=CC=C1OC(C)=O FEJKLNWAOXSSNR-UHFFFAOYSA-N 0.000 description 1
229960004277 benorilate Drugs 0.000 description 1
PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
150000001558 benzoic acid derivatives Chemical class 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
239000002439 beta secretase inhibitor Substances 0.000 description 1
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000006664 bond formation reaction Methods 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
229960003655 bromfenac Drugs 0.000 description 1
ZBPLOVFIXSTCRZ-UHFFFAOYSA-N bromfenac Chemical compound NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1 ZBPLOVFIXSTCRZ-UHFFFAOYSA-N 0.000 description 1
150000001649 bromium compounds Chemical class 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000004067 bulking agent Substances 0.000 description 1
KDKYADYSIPSCCQ-UHFFFAOYSA-N but-1-yne Chemical compound CCC#C KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
229960003184 carprofen Drugs 0.000 description 1
IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 description 1
239000000969 carrier Substances 0.000 description 1
229960000590 celecoxib Drugs 0.000 description 1
RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
230000030833 cell death Effects 0.000 description 1
230000011712 cell development Effects 0.000 description 1
230000024245 cell differentiation Effects 0.000 description 1
239000008004 cell lysis buffer Substances 0.000 description 1
230000010001 cellular homeostasis Effects 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
150000005829 chemical entities Chemical class 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960002688 choline salicylate Drugs 0.000 description 1
239000012501 chromatography medium Substances 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
235000013985 cinnamic acid Nutrition 0.000 description 1
229930016911 cinnamic acid Natural products 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
229960005228 clioquinol Drugs 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
230000019771 cognition Effects 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
238000002591 computed tomography Methods 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
229940111134 coxibs Drugs 0.000 description 1
239000006071 cream Substances 0.000 description 1
238000004132 cross linking Methods 0.000 description 1
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
229940097362 cyclodextrins Drugs 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
125000005534 decanoate group Chemical class 0.000 description 1
238000006114 decarboxylation reaction Methods 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
230000003831 deregulation Effects 0.000 description 1
229910052805 deuterium Inorganic materials 0.000 description 1
238000010586 diagram Methods 0.000 description 1
229960001259 diclofenac Drugs 0.000 description 1
DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
229960000616 diflunisal Drugs 0.000 description 1
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
CXQRZKIIGJLWPJ-UHFFFAOYSA-N diphenylphosphane;1-naphthalen-1-ylnaphthalene Chemical group C=1C=CC=CC=1PC1=CC=CC=C1.C1=CC=C2C(C=3C4=CC=CC=C4C=CC=3)=CC=CC2=C1 CXQRZKIIGJLWPJ-UHFFFAOYSA-N 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
229940120889 dipyrone Drugs 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
229960003530 donepezil Drugs 0.000 description 1
239000008298 dragée Substances 0.000 description 1
238000009510 drug design Methods 0.000 description 1
238000009513 drug distribution Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000522 effect on autophagocytosis Effects 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
235000020776 essential amino acid Nutrition 0.000 description 1
239000003797 essential amino acid Substances 0.000 description 1
235000004626 essential fatty acids Nutrition 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
229960005293 etodolac Drugs 0.000 description 1
XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
229960004945 etoricoxib Drugs 0.000 description 1
MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 1
229940108366 exelon Drugs 0.000 description 1
238000000605 extraction Methods 0.000 description 1
ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 description 1
229960001395 fenbufen Drugs 0.000 description 1
229960001419 fenoprofen Drugs 0.000 description 1
108090000062 ficolin Proteins 0.000 description 1
239000000945 filler Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000012530 fluid Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Chemical group 0.000 description 1
125000003709 fluoroalkyl group Chemical group 0.000 description 1
125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
229960002390 flurbiprofen Drugs 0.000 description 1
SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
150000004675 formic acid derivatives Chemical class 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
229960002598 fumaric acid Drugs 0.000 description 1
QORVDGQLPPAFRS-XPSHAMGMSA-N galantamine hydrobromide Chemical group Br.O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 QORVDGQLPPAFRS-XPSHAMGMSA-N 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000000499 gel Substances 0.000 description 1
238000007429 general method Methods 0.000 description 1
229960002518 gentamicin Drugs 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
229940097043 glucuronic acid Drugs 0.000 description 1
230000000848 glutamatergic effect Effects 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
229940074045 glyceryl distearate Drugs 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
125000003827 glycol group Chemical group 0.000 description 1
229960004275 glycolic acid Drugs 0.000 description 1
230000036541 health Effects 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
125000004446 heteroarylalkyl group Chemical group 0.000 description 1
125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 1
125000005844 heterocyclyloxy group Chemical group 0.000 description 1
KKLGDUSGQMHBPB-UHFFFAOYSA-N hex-2-ynedioic acid Chemical class OC(=O)CCC#CC(O)=O KKLGDUSGQMHBPB-UHFFFAOYSA-N 0.000 description 1
239000004312 hexamethylene tetramine Substances 0.000 description 1
235000010299 hexamethylene tetramine Nutrition 0.000 description 1
210000005260 human cell Anatomy 0.000 description 1
ZRJBHWIHUMBLCN-YQEJDHNASA-N huperzine A Chemical compound N1C(=O)C=CC2=C1C[C@H]1\C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-YQEJDHNASA-N 0.000 description 1
BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical group NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 1
ZUFVXZVXEJHHBN-UHFFFAOYSA-N hydron;1,2,3,4-tetrahydroacridin-9-amine;chloride Chemical compound [Cl-].C1=CC=C2C([NH3+])=C(CCCC3)C3=NC2=C1 ZUFVXZVXEJHHBN-UHFFFAOYSA-N 0.000 description 1
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
229960001680 ibuprofen Drugs 0.000 description 1
229950010480 icopezil Drugs 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
230000004957 immunoregulator effect Effects 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
229960000905 indomethacin Drugs 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
150000002484 inorganic compounds Chemical class 0.000 description 1
229910010272 inorganic material Inorganic materials 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
150000004694 iodide salts Chemical class 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
229940045996 isethionic acid Drugs 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical class CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
150000002540 isothiocyanates Chemical class 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
RPCVIAXDAUMJJP-PZBABLGHSA-N ispronicline Chemical compound CN[C@@H](C)C\C=C\C1=CN=CC(OC(C)C)=C1 RPCVIAXDAUMJJP-PZBABLGHSA-N 0.000 description 1
229950001646 ispronicline Drugs 0.000 description 1
DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
229960000991 ketoprofen Drugs 0.000 description 1
OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 1
229960004752 ketorolac Drugs 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
229960000448 lactic acid Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
201000010901 lateral sclerosis Diseases 0.000 description 1
229940033355 lauric acid Drugs 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
229960004338 leuprorelin Drugs 0.000 description 1
239000003446 ligand Substances 0.000 description 1
125000005647 linker group Chemical group 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
OXROWJKCGCOJDO-JLHYYAGUSA-N lornoxicam Chemical compound O=C1C=2SC(Cl)=CC=2S(=O)(=O)N(C)\C1=C(\O)NC1=CC=CC=N1 OXROWJKCGCOJDO-JLHYYAGUSA-N 0.000 description 1
229960002202 lornoxicam Drugs 0.000 description 1
229960002373 loxoprofen Drugs 0.000 description 1
BAZQYVYVKYOAGO-UHFFFAOYSA-M loxoprofen sodium hydrate Chemical compound O.O.[Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 BAZQYVYVKYOAGO-UHFFFAOYSA-M 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
229960000994 lumiracoxib Drugs 0.000 description 1
KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229940091250 magnesium supplement Drugs 0.000 description 1
238000011418 maintenance treatment Methods 0.000 description 1
229940049920 malate Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
150000002690 malonic acid derivatives Chemical class 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
229960003803 meclofenamic acid Drugs 0.000 description 1
239000002609 medium Substances 0.000 description 1
229960003464 mefenamic acid Drugs 0.000 description 1
HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
229960001929 meloxicam Drugs 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
125000005341 metaphosphate group Chemical group 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical class COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
229960001952 metrifonate Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
210000004688 microtubule Anatomy 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000003607 modifier Substances 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
208000005264 motor neuron disease Diseases 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
YCRCWHFFTTVANS-UHFFFAOYSA-N n-(4-acetylpiperazin-1-yl)-4-fluorobenzamide;hydrate Chemical compound O.C1CN(C(=O)C)CCN1NC(=O)C1=CC=C(F)C=C1 YCRCWHFFTTVANS-UHFFFAOYSA-N 0.000 description 1
SQAZQLMBEHYFJA-BTJKTKAUSA-N n-(benzo[b][1]benzoxepin-5-ylmethyl)-n-methylprop-2-yn-1-amine;(z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.C#CCN(C)CC1=CC2=CC=CC=C2OC2=CC=CC=C12 SQAZQLMBEHYFJA-BTJKTKAUSA-N 0.000 description 1
WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
USANJCUYKQTNCU-UHFFFAOYSA-N n-[[5-[[5-(4-chlorophenyl)sulfonylpyrazin-2-yl]amino]-1,3,4-thiadiazol-2-yl]methyl]acetamide Chemical compound S1C(CNC(=O)C)=NN=C1NC1=CN=C(S(=O)(=O)C=2C=CC(Cl)=CC=2)C=N1 USANJCUYKQTNCU-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
229960004270 nabumetone Drugs 0.000 description 1
229940033872 namenda Drugs 0.000 description 1
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
229960002009 naproxen Drugs 0.000 description 1
CMWTZPSULFXXJA-VIFPVBQESA-M naproxen(1-) Chemical compound C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-M 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229960002362 neostigmine Drugs 0.000 description 1
LULNWZDBKTWDGK-UHFFFAOYSA-M neostigmine bromide Chemical compound [Br-].CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 LULNWZDBKTWDGK-UHFFFAOYSA-M 0.000 description 1
OGZQTTHDGQBLBT-UHFFFAOYSA-N neramexane Chemical compound CC1(C)CC(C)(C)CC(C)(N)C1 OGZQTTHDGQBLBT-UHFFFAOYSA-N 0.000 description 1
229950004543 neramexane Drugs 0.000 description 1
229940000041 nervous system drug Drugs 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
229960000965 nimesulide Drugs 0.000 description 1
HYWYRSMBCFDLJT-UHFFFAOYSA-N nimesulide Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1=CC=CC=C1 HYWYRSMBCFDLJT-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
125000006574 non-aromatic ring group Chemical group 0.000 description 1
239000002687 nonaqueous vehicle Substances 0.000 description 1
238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical class CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
239000002674 ointment Substances 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
229960002969 oleic acid Drugs 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000008008 oral excipient Substances 0.000 description 1
239000007935 oral tablet Substances 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
150000002892 organic cations Chemical class 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
150000003891 oxalate salts Chemical class 0.000 description 1
229940116315 oxalic acid Drugs 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
229960003540 oxyquinoline Drugs 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
229940098695 palmitic acid Drugs 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
229960004662 parecoxib Drugs 0.000 description 1
TZRHLKRLEZJVIJ-UHFFFAOYSA-N parecoxib Chemical compound C1=CC(S(=O)(=O)NC(=O)CC)=CC=C1C1=C(C)ON=C1C1=CC=CC=C1 TZRHLKRLEZJVIJ-UHFFFAOYSA-N 0.000 description 1
YZPOQCQXOSEMAZ-UHFFFAOYSA-N pbt2 Chemical compound ClC1=CC(Cl)=C(O)C2=NC(CN(C)C)=CC=C21 YZPOQCQXOSEMAZ-UHFFFAOYSA-N 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
239000008063 pharmaceutical solvent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229950000688 phenothiazine Drugs 0.000 description 1
DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
229960002895 phenylbutazone Drugs 0.000 description 1
VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Chemical group 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
125000005498 phthalate group Chemical class 0.000 description 1
LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 1
229960001697 physostigmine Drugs 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229960002702 piroxicam Drugs 0.000 description 1
QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
229920001748 polybutylene Polymers 0.000 description 1
229940068918 polyethylene glycol 400 Drugs 0.000 description 1
DPNGIIPSQYKWQA-AVGNSLFASA-N posatirelin Chemical compound N([C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(N)=O)C(=O)[C@@H]1CCCC(=O)N1 DPNGIIPSQYKWQA-AVGNSLFASA-N 0.000 description 1
229950009321 posatirelin Drugs 0.000 description 1
108700042079 posatirelin Proteins 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
239000001294 propane Substances 0.000 description 1
KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical class CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
229940095574 propionic acid Drugs 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
239000000296 purinergic P1 receptor antagonist Substances 0.000 description 1
150000003216 pyrazines Chemical class 0.000 description 1
150000003217 pyrazoles Chemical class 0.000 description 1
USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical class C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
ZRJBHWIHUMBLCN-BMIGLBTASA-N rac-huperzine A Natural products N1C(=O)C=CC2=C1C[C@@H]1C(=CC)[C@@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-BMIGLBTASA-N 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000011347 resin Substances 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
229960004136 rivastigmine Drugs 0.000 description 1
RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
229960000371 rofecoxib Drugs 0.000 description 1
102220084927 rs778740017 Human genes 0.000 description 1
108010038196 saccharide-binding proteins Proteins 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
230000007017 scission Effects 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000000926 separation method Methods 0.000 description 1
235000021391 short chain fatty acids Nutrition 0.000 description 1
150000004666 short chain fatty acids Chemical class 0.000 description 1
230000011664 signaling Effects 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
238000003797 solvolysis reaction Methods 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
241000894007 species Species 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
229960004274 stearic acid Drugs 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
239000000758 substrate Substances 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
125000000565 sulfonamide group Chemical group 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
125000001174 sulfone group Chemical group 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
150000003461 sulfonyl halides Chemical class 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
229960000894 sulindac Drugs 0.000 description 1
229960004492 suprofen Drugs 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229950005628 tarenflurbil Drugs 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
229960002871 tenoxicam Drugs 0.000 description 1
WZWYJBNHTWCXIM-UHFFFAOYSA-N tenoxicam Chemical compound O=C1C=2SC=CC=2S(=O)(=O)N(C)C1=C(O)NC1=CC=CC=N1 WZWYJBNHTWCXIM-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 description 1
125000005323 thioketone group Chemical group 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
229960001017 tolmetin Drugs 0.000 description 1
UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
229960003570 tramiprosate Drugs 0.000 description 1
230000037317 transdermal delivery Effects 0.000 description 1
150000003918 triazines Chemical class 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
NFACJZMKEDPNKN-UHFFFAOYSA-N trichlorfon Chemical compound COP(=O)(OC)C(O)C(Cl)(Cl)Cl NFACJZMKEDPNKN-UHFFFAOYSA-N 0.000 description 1
229960002004 valdecoxib Drugs 0.000 description 1
LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
229940005605 valeric acid Drugs 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 0.000 description 1
PMBLXLOXUGVTGB-UHFFFAOYSA-N zanapezil Chemical compound C=1C=C2CCCCNC2=CC=1C(=O)CCC(CC1)CCN1CC1=CC=CC=C1 PMBLXLOXUGVTGB-UHFFFAOYSA-N 0.000 description 1
229950010696 zanapezil Drugs 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1